All more highly organized, multicellular, living systems, even man, cover the energy requirement of their living cells and tissue according to the principle of biological oxidation.
Carbohydrates, amino acids, fatty acids and nucleotides, on dehydrogenation (dehydrogenation=oxidation) give up by different metabolic pathways a portion of the chemical energy stored in these molecules and are finally supplied to the common final degradation in the citric acid cycle.
In the metabolic cycle of healthy cells or tissue, which represents the common final step for monosaccharides, fatty acids and amino acids, the C-6 compounds (citric acid) entering the cycle are broken down during one run in the cycle by two decarboxylation reactions to C-4 compounds (oxalacetic acid). In other words, the carbon chain is shortened by two carbon atoms.
In addition, 8 hydrogen atoms are oxidized in the citric acid cycle over the respiratory chain with production of energy to four molecules of water.
The hydrogen, obtained during dehydrogenations by various breakdown paths, is transported by hydrogen-transporting coenzymes NAD and FAD to the inner membrane of the mitochondria, the cell organelles, which are regarded as the power plants of a cell. With the structure-bound enzymes of the respiratory chain, the cytochromes, the hydrogen forms an electron transporting chain which--as also the whole of the metabolism--can function only if the hydrogen in the last element of the chain can react in a redox reaction with oxygen to form water. At a pH of 7, the normal potential E.sub.2 of this redox reaction is of the order of .+-.0.810 volt at a pH of 7, so that a drag is exerted on the electron transport chain.
Oxygen thus is the terminal hydrogen or electron acceptor in the metabolic process and, due to its presence, maintains the flow of electrons in the metabolism of a cell.
The respiratory chain in the mitochondria thus leads to a type of biochemical oxyhydrogen gas reaction, in which the respiratory substrates are dehydrogenated. The high reaction enthalpy, which is given off when water is formed from hydrogen and oxygen, is released gradually by the stepwise reaction of the hydrogen or the electrons over a cascade of intermediate carriers and a considerable proportion is stored in the form of chemical energy as adenosine triphosphate (ATP) for energy-consuming cell reactions.
Every healthy cell, which has mitochondria, covers its energy requirements in this fashion. The number of mitochondria per cell varies between 10.sup.2 and 6.times.10.sup.3, depending on the metabolic tasks, and their oxygen requirement is also correspondingly different.
In every second of the life of a living, oxidizing system, oxygen must be available to a sufficient extent in the mitochondria of all living cells. Required for this is a steady, undisturbed flow of oxygen from the respired air with an adequate partial pressure of oxygen over the respiratory passages, the transfer of oxygen at the lung-blood barrier of the lung alveoli, the diffusion through the erythrocyte membrane, the oxyhemoglobin formation and the detachment form hemoglobin in the blood capillaries of the tissue, the oxygen diffusion through the intercellular space, the interstitial space, through the cell membrane and the mitochondrial membrane up to the above-described respiratory chain. A long, but important path of the oxygen.
This oxidation, which takes place constantly undisturbed in all cells, is the important prerequisite for maintaining the health of the organism. In an approximate comparison with electrical or electronic components and their circuits, it is possible to speak of the operating characteristic curve of a healthy cell. On this curve, there is an optimum operating point, which may shift only slightly on the operating characteristic curve. If the operating point is impermissibly far removed from its optimum, then this is an indication of an appreciable malfunction of the metabolism of the cell. Such a malfunction is caused, for example, by the phenomenon of hyperoxidation, whicn is also referred to as oxidative stress. The oxidative stress may arise either through an excessive supply of activated oxygen steps (oxygen radicals) and/or through a decrease in those molecules, which normally are capable of intercepting this radical energy and are referred to as scavenger molecules. If the cells are incapable of eliminating this malfunction by their own efforts, destruction of biomolecules and cell structures, such as lipid peroxidation of the cell membranes, as well as diverse cell malfunctions, cancerous degeneration of a cell and finally cell destruction take place.
In living systems, nature had to protect its molecular and cell structures from the very start against the action of destructive oxygen radicals, which are constantly formed by exogenous noxious agents and also in cell metabolism. For this purpose, it developed protective enzymes and protective molecules as scavengers, which are capable of intercepting these radicals reliably and quickly.
As a consequence of the inability of the individual malfunctioning cells to intercept the energy-rich radicals, diseases may arise such as cancer of any origin, malignant diseases of blood cells, hepatopathies, fatty degeneration of the liver, fatty cirrhosis, liver cirrhoses of any origin, malfunctions of immunological defense functions in the area of natural killer cells, complex malfunctions of the lymphokine biosynthesis in the T helper cells, cardiomyopathies of any origin, neurological diseases of inflammatory, allergic or degenerative origin, blood cell diseases, injuries to the eye lens, proliferation and differentiation disorders of epithelial and endothelial tissue and of mucous membrane tissue and many more. The type of disease that will occur depends mainly on which cells or cell tissues are affected most severely.
It follows from this that oxidations, which are necessarily essential to the living systems, must not lead to hyperoxidations.
From a chemical point of view, oxidation means:
1. emission of electrodes, PA1 2. emission of hydrogen, PA1 3. absorption of oxygen. PA1 1. absorption of electrons PA1 2. absorption of hydrogen, PA1 3. emission of oxygen.
Correspondingly, reduction means:
Thermodynamically all reductions are endothermic processes and all oxidations exothermic processes. This means that the oxidized stage is in a lower energy state than the reduced state. The reduced stage can emit "energy"=electrons and the oxidized stage is reduced by the "absorption of energy", that is, by the absorption of electrons.
The basis for all the reductive power in the blood and in most of the cells of man and mammals is the reduced form of the tripeptide, glutathione (G--SH) consisting of the three amino acids, glutamic acid, cystaine and glycine with the following structure formula: ##STR1##
The functionality of living systems, which is based on the principle of biological oxidation, is possible only due to the existence of a reductive protection by this important molecule, G--SH.
By dehydrogenation or oxidation, two molecules of reduced glutathione (G--SH) can be converted into one molecule of oxidized glutathione (G--S--S--G) with the formation of a disulfide bond. ##STR2##
In numerous observations, it was possible to observe that cells, which fulfill their specific function perfectly, have a concentration ratio of reduced glutathione (G--SH) to oxidized glutathione (G--S--S--G) of about 400 to 1. This means that the intact, viable cell has a high reductive potential in the form of the reduced glutathione content. The concentration ratio of G--SH to G--S--S--G in the area of 400 to 1 can be taken as an indicator of the optimal functioning and of the reliable maintenance of the structure of the cell.
The reductive potential of the reduced glutathione, that is, the optimum, high, intracellular concentration of this material, is of the utmost importance for maintaining the functionality of many and perhaps even all enzymes of the cell metabolism, for preventing oxidative changes in the catalytic and allosteric centers of the enzymes and for maintaining their optimum conformation.
All presently existing classical therapies support either the phenomenon of oxidation, that is, the oxidative side of living systems, or, through drugs which, as xenobiotics, require oxidation for their degradation and for metabolite formation, intervene in the "oxidative power" of the metabolism, such as the cytochrome-p-450 system and drug degradation.